The effect of methylprednisolone on constitutive and interferon-beta (IFN-beta) induced HLA-DR expression on monocytes from multiple sclerosis (MS) patients was investigated. Constitutive HLA-DR expression was reduced by 50% following a single dose (500 mg) of intravenous methylprednisolone (IVMP). Stimulation with natural IFN-beta, in vitro, resulted in a 20 fold increase in HLA-DR expression. Following IVMP, IFN-beta inducible HLA-DR levels were reduced (non-significantly) by 20-30%. Experiments in which monocytes from normal subjects and MS patients were pre-treated in vitro with methylprednisolone prior to IFN-beta stimulation revealed that induction of HLA-DR was significantly inhibited; in contrast, IFN-beta induced HLA-DR expression was not down-regulated following subsequent in vitro treatment with methylprednisolone. These findings suggest that the immunomodulatory effects of IVMP could be attenuated in MS patients receiving regular IFN-beta therapy.